Cell and Gene Therapy for Patients Suffering from Xerostomia (Dry Mouth): Positioning Extracellular Vesicles as the Bridge Between Biomarker Discovery and Regenerative Therapy in Xerostomia-A Scoping Review.

Xerostomia is a common and debilitating condition caused by salivary gland dysfunction, frequently associated with primary Sjögren's syndrome and head and neck radiotherapy. Current management is largely symptomatic and does not address underlying glandular injury. Extracellular vesicles (EVs), including exosomes, have emerged as candidate mediators of intercellular communication that have been proposed for diagnostic and therapeutic applications; however, their translational relevance to xerostomia remains uncertain and is currently supported only by exploratory evidence. This scoping review aimed to map and interpret current evidence on EV-based approaches in xerostomia and salivary gland dysfunction. A scoping review was conducted in accordance with "Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR)" checklist. Twenty-five articles were included, comprising 14 primary studies and 11 review articles. Studies were analysed based on application focus, methodological characteristics, reported outcomes, and translational readiness. Most primary studies focused on EVs as diagnostic biomarkers or their roles in immune-epithelial signalling. Therapeutic research was limited and largely confined to human-relevant translational models, namely human peripheral blood mononuclear cell (PBMC) assays and freshly resected human salivary gland tissue-maintained ex vivo. Outcomes were predominantly molecular and cellular, with minimal assessment of salivary flow or patient-reported symptoms. The current evidence base, although biologically plausible, remains exploratory: most included studies are mechanistic, and no clinical efficacy studies in xerostomia were identified. A substantial gap therefore persists between molecular findings and clinically meaningful outcomes, and further translational research is required before any conclusions can be drawn regarding the clinical utility of EV-based approaches.